Cancer remains one of the most formidable global health challenges, demanding innovative and multidisciplinary approaches for effective diagnosis and treatment. This special issue explores the convergence of bio-engineered polymeric systems, organ-on-a-chip (OoC) platforms, and phytochemistry-driven therapeutics as transformative tools in cancer theranostics. Recent advances in smart polymeric nanocarriers—including stimuli-responsive hydrogels, biodegradable nanoparticles, and biopolymer-based drug delivery systems—have opened new horizons for targeted and controlled release of both synthetic and plant-derived anticancer agents. Simultaneously, organ-on-a-chip microfluidic platforms are revolutionizing preclinical cancer modeling by faithfully recapitulating the tumor microenvironment, enabling high-throughput drug screening, and facilitating personalized therapeutic strategies. By bridging phytochemistry with precision oncology, this special issue aims to highlight cutting-edge research that integrates natural bioactive compounds into engineered delivery platforms and biomimetic in vitro models. We invite original research articles, comprehensive reviews, and perspective papers that advance our understanding of these interdisciplinary frontiers, ultimately accelerating the translation of laboratory innovations into clinically viable cancer theranostic solutions.